Neuropilins have recently been characterized as receptors for secreted semaphorins. The present invention provides a dominant negative form of neuropilin-1 comprising a deletion construct of one of its extracellular domains. Expression of this variant in cultured primary sympathetic neurons blocks the paralysis of growth cone motility normally induced by SEMA-3A (collapsin-1, semaphorin III, semaphorin D) and SEMA-3C (collapsin-3, semaphorin E), but not that induced by SEMA-3F (semaphorin IV). Other truncated forms of neuropilin-1, such as a variant missing the cytoplasmic domain, fail to act as a dominant negative receptor component. Thus, overexpression of dominant negative neuropilins provide a powerful new method of blocking the functions of selected secreted semaphorins, as demonstrated by the modulation of olfactory axon trajectory in a developing animal model.
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